During the Clone Wars Rex was in command of Torrent Company of the famed 501st Legion. Rex and his men were assigned to patrol the sectors of the galaxy within the Outer Rim. Anakin Skywalker's second in command during the Clone Wars, Captain Rex was a freethinking, tough, and aggressive clone trooper. Rex voiced his professional opinions to even the highest-ranking Jedi.

Rex fought alongside Generals Kenobi and Skywalker at the Battle of Christophsis, and then led Torrent Company at the Battle of Teth. Rex and his men held off Asajj Ventress' droid armies long enough for Anakin Skywalker and Ahsoka Tano to escape Teth with Rotta the Hutt. He engaged against several droids in a courtyard at the monastery. Although Torrent Company was reduced to six men during the battle, Rex and his soldiers held off an entire droid army long enough for General Kenobi to arrive with the 212th Attack Battalion. Rex understood Anakin's decision to head to Tatooine, as the mission always came first to him.

Rex would later lead a group of rookies along with Commander Cody to take back a communications station on the Rishi moon. He created the plan to get the droids to open the door by pretending to be one of the droids in clone armor. After using a severed droid head to fool the guard he blasted the droid in the head and proceeded to fight and ultimately kill the droid commander by snapping his neck. Unfortunately, a droid invasion force led by General Grievous arrived to take the outpost. To give the Republic notice that the moon has been compromised, they resolved to blow the outpost up with liquid tibanna. Rex tried to prime one of the detonators but it didn't work. Shinie Hevy stayed behind to fix it but failed. With droid forces overwhelming the base, Hevy made the ultimate sacrifice by manually detonating the bomb, destroying the outpost and alerting the Republic. Rex then inducted clone troopers Echo and Fives into the 501st Legion.

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